Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  24 WSVEHPQTLFAWEGACIQIPCKYKVPKprSRLDSILLFQNYTFDNTTRDFTGKVLYNNTkasiETELYFSQQDRVTFLGN 103
Cdd:cd20929    1 WVFEHPETLYAWEGACVWIPCTYRALD--GDLESFILFHNPEYNKATSKFDGTRLYEST----KDGKVPSEQKRVQFLGD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 672035735 104 RSNNCTLKIDPIHANDSGKLGLRLISGTDKWMEHIHLNVS 143
Cdd:cd20929   75 KNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 114

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 246 PKLQITVNPTE--VKEGNSVTMTCQVNSSNPSLSTkkVSWFKDGSFLKEQQEQEeLTLHSVTKDMRGKYQCRASNNIGQG 323
Cdd:cd20937    1 PKLEIKVTPSDaiVREGDSVTMTCEVSSSNPEYTT--VSWLKDGTSLKKQNTFT-LNLREVTKDQSGKYCCQVSNDVGPG 77

                         90
                 ....*....|.
gi 672035735 324 QSKEVALTVLY 334
Cdd:cd20937   78 RSEEVFLQVQY 88

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735   523 EIHAGQHVLLQCDFSGSFPTEVRFFWKKNGNLVQEGRY----------LNFSSISPEDSGNYNCMVRNSIGETSSQAWsL 592
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGTT-L 83

                   ..
gi 672035735   593 QV 594
Cdd:smart00410  84 TV 85

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 672035735 424 PKAVTTVIQSVTPIREGDSVTLDCRYNSSNPEVTKYEWSPQGS 466
Cdd:cd20937    1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGT 43

First immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the V-set of IgSF domains; The members here are composed of the first immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the V-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  24 WSVEHPQTLFAWEGACIQIPCKYKVPKprSRLDSILLFQNYTFDNTTRDFTGKVLYNNTkasiETELYFSQQDRVTFLGN 103
Cdd:cd20929    1 WVFEHPETLYAWEGACVWIPCTYRALD--GDLESFILFHNPEYNKATSKFDGTRLYEST----KDGKVPSEQKRVQFLGD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 672035735 104 RSNNCTLKIDPIHANDSGKLGLRLISGTDKWMEHIHLNVS 143
Cdd:cd20929   75 KNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 114

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 246 PKLQITVNPTE--VKEGNSVTMTCQVNSSNPSLSTkkVSWFKDGSFLKEQQEQEeLTLHSVTKDMRGKYQCRASNNIGQG 323
Cdd:cd20937    1 PKLEIKVTPSDaiVREGDSVTMTCEVSSSNPEYTT--VSWLKDGTSLKKQNTFT-LNLREVTKDQSGKYCCQVSNDVGPG 77

                         90
                 ....*....|.
gi 672035735 324 QSKEVALTVLY 334
Cdd:cd20937   78 RSEEVFLQVQY 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  335 PPepsKVHIYPSP--AEEGQSVELICDSLASPRATnYTWYHNGEMVPGASHEK---------LQISNVSLWHAGKYSCLA 403
Cdd:pfam13927   1 KP---VITVSPSSvtVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSrslsgsnstLTISNVTRSDAGTYTCVA 76

                  ..
gi 672035735  404 EN 405
Cdd:pfam13927  77 SN 78

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735   523 EIHAGQHVLLQCDFSGSFPTEVRFFWKKNGNLVQEGRY----------LNFSSISPEDSGNYNCMVRNSIGETSSQAWsL 592
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGTT-L 83

                   ..
gi 672035735   593 QV 594
Cdd:smart00410  84 TV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  514 KILKVSPASEIHAGQHVLLQCDFSGSFPTEVRffWKKNGNLVQEGRYLNF-----------SSISPEDSGNYNCMVRNSI 582
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVS--WFKDGQPLRSSDRFKVtyeggtytltiSNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|..
gi 672035735  583 GETSSQAwSLQV 594
Cdd:pfam07679  80 GEAEASA-ELTV 90

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735   348 AEEGQSVELICDSLASPRATnYTWYHNG----------EMVPGASHEKLQISNVSLWHAGKYSCLAENRLgcGKIEQEAE 417
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPE-VTWYKQGgkllaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS--GSASSGTT 82

                   ...
gi 672035735   418 LDV 420
Cdd:smart00410  83 LTV 85

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735   610 SVMEGKKATLSCESDAHPPVFKYiWFDANDQDLHFSG----------QKLRLEPLRVQHTGSYRCQGINELGTGKSpPST 679
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVT-WYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASS-GTT 82

                   ...
gi 672035735   680 LTV 682
Cdd:smart00410  83 LTV 85

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 672035735 424 PKAVTTVIQSVTPIREGDSVTLDCRYNSSNPEVTKYEWSPQGS 466
Cdd:cd20937    1 PKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGT 43

First immunoglobulin domain of Cluster of Differentiation (CD) 22; member of the V-set of IgSF domains; The members here are composed of the first immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the V-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  24 WSVEHPQTLFAWEGACIQIPCKYKVPKprSRLDSILLFQNYTFDNTTRDFTGKVLYNNTkasiETELYFSQQDRVTFLGN 103
Cdd:cd20929    1 WVFEHPETLYAWEGACVWIPCTYRALD--GDLESFILFHNPEYNKATSKFDGTRLYEST----KDGKVPSEQKRVQFLGD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 672035735 104 RSNNCTLKIDPIHANDSGKLGLRLISGTDKWMEHIHLNVS 143
Cdd:cd20929   75 KNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVS 114

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 246 PKLQITVNPTE--VKEGNSVTMTCQVNSSNPSLSTkkVSWFKDGSFLKEQQEQEeLTLHSVTKDMRGKYQCRASNNIGQG 323
Cdd:cd20937    1 PKLEIKVTPSDaiVREGDSVTMTCEVSSSNPEYTT--VSWLKDGTSLKKQNTFT-LNLREVTKDQSGKYCCQVSNDVGPG 77

                         90
                 ....*....|.
gi 672035735 324 QSKEVALTVLY 334
Cdd:cd20937   78 RSEEVFLQVQY 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  246 PKLQITVNPTEVKEGNSVTMTCQVNSSNPSlstkKVSWFKDGSFLKEQQEQEE--------LTLHSVTKDMRGKYQCRAS 317
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPP----TITWYKNGEPISSGSTRSRslsgsnstLTISNVTRSDAGTYTCVAS 77

                  .
gi 672035735  318 N 318
Cdd:pfam13927  78 N 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  335 PPepsKVHIYPSP--AEEGQSVELICDSLASPRATnYTWYHNGEMVPGASHEK---------LQISNVSLWHAGKYSCLA 403
Cdd:pfam13927   1 KP---VITVSPSSvtVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSrslsgsnstLTISNVTRSDAGTYTCVA 76

                  ..
gi 672035735  404 EN 405
Cdd:pfam13927  77 SN 78

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. Ig Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 149 PYIQLPSEIRESQRVSLTCGLNFTCFGYDISLRWSldGSEVSPVTSSITSSVENVYT--ESKLTFQPKWTDHGKSMMCQV 226
Cdd:cd20987    1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEFSWL--GAALTPLPPVLGRLEEEGTTthSSVLTFTPRPEDHGTNLTCQV 78

                         90
                 ....*....|....*.
gi 672035735 227 -WHFSQVLSERTVRLD 241
Cdd:cd20987   79 kFPGATVTTERTIQLN 94

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 246 PKLQITVNPTeVKEGNSVTMTCQVNSSNPSLSTKkvsWFKDGSFLKEQQEQE----------ELTLHSVTKDMRGKYQCR 315
Cdd:cd05750    1 PKLKEMKSQT-VQEGSKLVLKCEATSENPSPRYR---WFKDGKELNRKRPKNikirnkkknsELQINKAKLEDSGEYTCV 76

                         90
                 ....*....|.
gi 672035735 316 ASNNIGQGQSK 326
Cdd:cd05750   77 VENILGKDTVT 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672035735  344 YPSPAEEGQSVELICDSLASPRAtNYTWYHNGEMVPgaSHEKLQISNVSLWHAGKYSCLAENRLGCGK 411
Cdd:pfam13895   7 SPTVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAIS--SSPNFFTLSVSAEDSGTYTCVARNGRGGKV 71

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  514 KILKVSPASEIHAGQHVLLQCDFSGSFPTEVRffWKKNGNLVQEGRYLNF-----------SSISPEDSGNYNCMVRNSI 582
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVS--WFKDGQPLRSSDRFKVtyeggtytltiSNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|..
gi 672035735  583 GETSSQAwSLQV 594
Cdd:pfam07679  80 GEAEASA-ELTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 672035735  519 SPASEIHAGQHVLLQCDFSGSFPTEVRffWKKNGNLVQEGRYLNFSSISPEDSGNYNCMVRNSIGETSSQAWSLQV 594
Cdd:pfam13895   6 PSPTVVTEGEPVTLTCSAPGNPPPSYT--WYKDGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 672035735 263 VTMTCQVNSSNPSlstkKVSWFKDGSFLKEQQEQE--------ELTLHSVTKDMRGKYQCRASNNIGQGQSKEV 328
Cdd:cd00096    1 VTLTCSASGNPPP----TITWYKNGKPLPPSSRDSrrselgngTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 672035735 530 VLLQCDFSGSFPTEVRffWKKNGNLVQEGRY-----------LNFSSISPEDSGNYNCMVRNSIGETSS 587
Cdd:cd00096    1 VTLTCSASGNPPPTIT--WYKNGKPLPPSSRdsrrselgngtLTISNVTLEDSGTYTCVASNSAGGSAS 67

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 257 VKEGNSVTMTCQVNSS-NPSlstkkVSWFKDGSFLKEQQEQEE-------LTLHSVTKDMRGKYQCRASNNIGQGQSKEV 328
Cdd:cd20970   14 AREGENATFMCRAEGSpEPE-----ISWTRNGNLIIEFNTRYIvrengttLTIRNIRRSDMGIYLCIASNGVPGSVEKRI 88

                 ....
gi 672035735 329 ALTV 332
Cdd:cd20970   89 TLQV 92

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 255 TEVKEGNSVTMTCQVnSSNPSlstKKVSWFKDGSFLKEQQEQEELTLHSVT-----KDMRGKYQCRASNNIGQGQSkEVA 329
Cdd:cd20978   11 VVVKGGQDVTLPCQV-TGVPQ---PKITWLHNGKPLQGPMERATVEDGTLTiinvqPEDTGYYGCVATNEIGDIYT-ETL 85

                 ...
gi 672035735 330 LTV 332
Cdd:cd20978   86 LHV 88

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 524 IHAGQHVLLQCDFSGSfPTEvRFFWKKNGNLVQE-GR---------------YLNFSSISPEDSGNYNCMVRNSIGETSS 587
Cdd:cd20956   13 LQPGPSVSLKCVASGN-PLP-QITWTLDGFPIPEsPRfrvgdyvtsdgdvvsYVNISSVRVEDGGEYTCTATNDVGSVSH 90

                 ...
gi 672035735 588 QAW 590
Cdd:cd20956   91 SAR 93

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 250 ITVNP--TEVKEGNSVTMTCQVNSSNPSLSTKkvsWFKDGSFLKEQqeQEELTLHSVTKDMRGKYQCRasnNIGQGQSKE 327
Cdd:cd05752    3 VSLDPpwTTVFQGEKVTLTCQGFYSPEQNSTQ---WYHNGTLISST--SSSYRIVAATVNDSGEYRCQ---TQGSSLSDP 74

                 ....*
gi 672035735 328 VALTV 332
Cdd:cd05752   75 VHLEV 79

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 350 EGQSVELICDSLASPrATNYTWYHNGEMV-PGASHEKLQ---------ISNVSLWHAGKYSCLAENRlgCGKIEQEAELD 419
Cdd:cd05744   14 EGRLCRFDCKVSGLP-TPDLFWQLNGKPVrPDSAHKMLVrengrhsliIEPVTKRDAGIYTCIARNR--AGENSFNAELV 90

                 .
gi 672035735 420 V 420
Cdd:cd05744   91 V 91

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735   610 SVMEGKKATLSCESDAHPPVFKYiWFDANDQDLHFSG----------QKLRLEPLRVQHTGSYRCQGINELGTGKSpPST 679
Cdd:smart00410   5 TVKEGESVTLSCEASGSPPPEVT-WYKQGGKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASS-GTT 82

                   ...
gi 672035735   680 LTV 682
Cdd:smart00410  83 LTV 85

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, organized as an extracellular module composed of Ig-like domains, an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains, followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735  24 WSVEHPQTLFAWEGACIQIPCKYKVPKPRSRLDSIllfQNYTFDNTTRDFTGKVLYNNTKASIETElyfSQQDRVTFLGN 103
Cdd:cd05712    1 WGLQMPKSVTVQEGLCVLIPCSFSYPADYWVSNPV---HGYWYRGGPYPKYRPPVATNNRTREVHE---STQGRFRLLGD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 672035735 104 RS-NNCTLKIDPIHANDSGKLGLRL-ISGTDKWM-EHIHLNVS 143
Cdd:cd05712   75 PGkKNCSLSISDARPEDSGKYFFRVeRGDSNKYSyLSNQLSLT 117

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 337 EPSKVhIYPSPAEEGQsVELICDSLASPRATnYTWYHNG---EMVPGASHE----KLQISN-VSLWHAGKYSCLAENRLG 408
Cdd:cd05850    8 QPSST-LFPEGSAEEK-VTLACRARASPPAT-YRWKMNGtelKMEPDSRYRlvagNLVISNpVKAKDAGSYQCLASNRRG 84

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672035735 248 LQITVNPTE--VKEGNSVTMTCQVnSSNPslsTKKVSWFKDGSFL-----KEQQEQEELTLHSVTKDMRGKYQCRASNNI 320
Cdd:cd20957    2 LSATIDPPVqtVDFGRTAVFNCSV-TGNP---IHTVLWMKDGKPLghssrVQILSEDVLVIPSVKREDKGMYQCFVRNDG 77

                 ....*
gi 672035735 321 GQGQS 325
Cdd:cd20957   78 DSAQA 82